Julie B. Dumond, PharmD, BCPS, AAHIVE, Research Assistant Professor in the Division of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy, is a pharmacist with strong training and background in patient-oriented research methodology, and a proven commitment to applying these methods to improving antiretroviral (ARV) use in HIV-infected patients. The candidate's long-term-career goal is to be an independently funded, academic pharmacometrician, with a rich and diverse experience in pharmacokinetic/pharmacodynamic modeling of antiretroviral drugs. In particular, the candidate will pursue prospective population pharmacokinetic/pharmacodynamic (PK/PD) data collection, with the goal of quantifying age-related factors that influence drug response and toxicity. The candidate's short-term career goals fostered by this career development award are 1) to obtain formal training in advanced PK/PD, biostatistics, and computational methods, 2) to gain hands-on experience in population PK/PD modeling, 3) to foster working relationships with leading pharmacometricians, 4) to develop the preliminary data for an R34/U01 or R01 application, and 5) to expand her training in the responsible training of research. The proposed research plan, career development activities, and mentorship team are all uniquely suited to assist the applicant in achieving these goals. The research plan is built around the central hypothesis that: 1) altered ARV pharmacokinetics contributes to altered pharmacodynamics as measured by clinical response and toxicity, and 2) chronological age may only partly explain alterations in pharmacokinetics, and subsequently, pharmacodynamics. In this proposal, we will develop a pharmacokinetic and a pharmacokinetic/pharmacodynamic model in two specific aims for two common ARV regimens, emtricitabine/tenofovir/efavirenz (Atripla) and emtricitabine/tenofovir/atazanavir/ritonavir (Truvada, Reyataz, and Norvir). To accomplish these aims, we will use optimal sample design simulation to prospectively collect drug concentration and drug response data from HIV-infected adults receiving the regimens of interest. Subjects will be recruited from the University of North Carolina (UNC) Clinical HIV Cohort. To support the candidate's career development, she will pursue advanced coursework and independent study in the areas of pharmacokinetic and pharmacodynamic theory and modeling, biostatistics, computational methods, and research ethics, in concert with hands-on modeling training. The mentorship team, which includes internationally-recognized, independently-funded investigators with expertise in ARV clinical pharmacology (Kashuba), pharmacometrics (Forrest), and HIV clinical care and research (Cohen), will guide Dr. Dumond's research, training, and professional development. The research environment including the NIH-funded Translational and Clinical Sciences Institute and Center for AIDS Research at UNC and the Department of Pharmaceutical Sciences at the University at Buffalo, State University of New York, will provide a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. NARRATIVE By 2015, more than 50% of the HIV-infected population in the United States will be at least 50 years of age, and little is known about the optimal clinical care of aging HIV-infected patients. The goal of this and subsequent research is to identify patient-specific factors modifying antiretroviral response and toxicity. This could lead to specific treatment recommendations for older HIV-infected patients.